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Abstract Objectives--To investigate the actual time of onset of osteonecrosis (ON) after high dose corticosteroid treatment in systemic lupus erythematosus (SLE). Methods--72 patients with active SLE, who received high dose [...]

The Australia High Court ruled in Commissioner of Taxation v. Peabody that the Commissioner had not established that the taxpayer should be liable for income tax on a stock transfer that involved a company owned by a family trust. The High Court also considered the scope of the Commissioner's discretion in determining whether a transaction constitutes a scheme entered into for tax avoidance purposes. Further decisions will be needed to clarify the continued vitality of the anti-avoidance provisions of Income Tax Assessment Act 1936 Part IVa.

The Taxation Laws Amendment Act of 1992 has changed the Australian tax system in regard to depreciation, rollovers, inter-corporate dividend rebates as well as income tax assessment. The main change relating to depreciation is in the shift of the responsibility for determining the effective life of depreciable assets from the government to the taxpayer.

100 Facetterminated nanocrystalline and 100 textured largegrained polycrystalline diamond PCD have been grown simultaneously not only on different substrates but also on the same substrate from a single deposition run using highpower microwave plasma chemical vapor deposition MPCVD. The synthesis of diamond with varying morphologies in the same deposition run was achieved by combining the effect of nitrogen addition on diamond growth and the influence of substrate size and geometry on the distribution of the plasma power density and temperature along the substrate. We have modeled the temperature distribution on the substrates by computer simulations using the finite element method. The formation mechanism of several morphologies including both 100 facetterminated nanocrystalline and 100 textured largegrained PCD on one substrate is discussed based on this temperature analysis and other simulation results described in the literature.

We investigated the effect of progesterone on the nerve during lengthening of the limb in rats. The sciatic nerves of rats were elongated by leg lengthening for ten days at 3 mm per day. On alternate days between the day after the operation and nerve dissection, the progesterone-treated group received subcutaneous injections of 1 mg progesterone in sesame oil and the control group received oil only. On the fifth, tenth and 17th day, the sciatic nerves were excised at the midpoint of the femur and the mRNA expression level of myelin protein P0 was analysed by quantitative real time polymerase chain reaction. On day 52 nodal length was examined by electron microscopy, followed by an examination of the compound muscle action potential (C-MAP) amplitude and the motor conduction velocity (MCV) of the tibial nerve on days 17 and 52. The P0 (a major myelin glycoprotein) mRNA expression level in the progesterone-treated group increased by 46.6% and 38.7% on days five and ten, respectively. On day 52, the nodal length in the progesterone-treated group was smaller than that in the control group, and the MCV of the progesterone-treated group had been restored to normal.Progesterone might accelerate the restoration of demyelination caused by nerve elongation by activating myelin synthesis.

Two indole-containing substrate analogues, in which a C20 isoprene unit is connected to indole (3-(geranylgeranyl)indole and 3-(farnesyldimethylallyl)indole), were synthesized and tested for enzymatic cyclization by squalene:hopene cyclase from Alicyclobacillus acidocaldarius. Interestingly, 3-(geranylgeranyl)indole was not a substrate for the bacterial squalene cyclase, while 3-(farnesyldimethylallyl)indole was efficiently converted to a 2:1 mixture of unnatural novel products.

The amount of platinum in the catalyst for the electrodes of polymer electrolyte fuel cells must be minimized to widely substitute this new energy system for conventional ones. In this study, a platinum-free catalyst for the cathodic oxygen reduction was formed from a natural organic compound, catalase. We carbonized catalase to produce a catalyst active in the superacidic atmosphere of the polymer electrolyte. Nitrogen adsorption onto the carbonized material revealed that the material had highly developed internal nanospaces, which were essential for exposing active sites to oxygen reduction on the pore surface. The carbonized material was also characterized by X-ray photoelectron spectroscopy, X-ray diffraction, transmission electron microscopy, and Mössbauer spectroscopy. The activity for oxygen reduction was evaluated using rotating disk electrodes, forming a catalyst layer from the carbonized material and the polymer electrolyte on the electrode surface and immersing the layer in oxygen-saturated perchloric acid. The activity increased with the increase in the specific surface area and possibly the increase in the activity of the respective active sites. A preliminary fuel cell test using the material in the cathode confirmed the electricity generation, although the performance was inferior to a Pt-based fuel cell.

1-Methylidenesqualene and 25-methylidenesqualene were converted to 30-methylidenehop-22(29)-ene by squalene:hopene cyclase from Alicyclobacillus acidocaldarius. It was remarkable that both analogues generated the same product. The hopanyl intermediate cation, stabilized by the methylidene residue, enabled a rotation of the isobutenyl group at C-21 prior to the final proton elimination. In contrast, in the formation of hop-22(29)-ene, the final proton abstraction takes place regiospecifically from the Z-methyl group, which was verified by cyclization of (1,1,1,24,24,24-²H6)squalene into (23,23,23,30,30,30-²H6)hop-22(29)-ene.

In the chalcone synthase (CHS) enzyme reaction, both the starter molecule and the extension unit of the poyketide chain elongation reaction were simultaneously replaced with nonphysiological substrates. When incubated with benzoyl-CoA and methylmalonyl-CoA as substrates, recombinant CHS from Scutellaria baicalensis afforded an unnatural novel triketide, 4-hydroxy-3,5-dimethyl-6-phenyl-pyran-2-one, along with a tetraketide, 4-hydroxy-3,5-dimethyl-6-(1-methyl-2-oxo-2-phenyl-ethyl)-pyran-2-one. On the other hand, the enzyme also accepted hexanoyl-CoA and methylmalonyl-CoA as substrates to produce an unnatural novel triketide, 4-hydroxy-3,5-dimethyl-6-pentyl-pyran-2-one.

Substrate specificities of plant polyketide synthases (PKSs) were investigated using analogues of malonyl-CoA, the extension unit of the polyketide chain elongation reactions. When incubated with methylmalonyl-CoA and 4-coumaroyl-CoA, plant PKSs (chalcone synthase from Scutellaria baicalensis, stilbene synthase from Arachis hypogaea, and benzalacetone synthase from Rheum palmatum) afforded an unnatural C6−C5 aromatic polyketide, 1-(4-hydroxyphenyl)pent-1-en-3-one, formed by one-step decarboxylative condensation of the two substrates. In contrast, succinyl-CoA was not accepted as a substrate by the enzymes.

Ellagitannins isolated from various plant sources as well as newly synthesized n-alkyl (C1−C18) esters of hexahydroxydiphenyl (HHDP) dicarboxylic acid were evaluated as enzyme inhibitors of recombinant rat squalene epoxidase, a rate-limiting enzyme of cholesterol biosynthesis. Among the ellagitannins tested, pedunculagin (IC50 = 2.0 μM) and eugeniin (IC50 = 1.6 μM), both containing (S)-HHDP ester group(s), showed remarkable inhibition, which was more potent than those of previously reported substrate analogue inhibitors. Furthermore, ellagic acid (IC50 = 2.0 μM), a bislactone formed by hydrolytic release of a HHDP group from ellagitannins, was also a good inhibitor of the enzyme. On the other hand, the synthetic HHDP esters with C6 (IC50 = 0.93 μM) and C8 alkyl side chains (IC50 = 0.83 μM) showed potent enzyme inhibition at the submicromolar concentration range, while esters with shorter chain lengths (C1−C4) and a C18 ester exhibited moderate inhibition (IC50 = 8−47 μM).

We compared the effects of nilvadipine, a calcium antagonist, and terazosin, an alphal blocker, on the hemodynamics and quality of life (QOL) in 12 elderly hypertensive patients with stroke. Following a washout period of 2 weeks, nilvadipine or terazosin was administered for 2 weeks in a randomized crossover manner. At the end of control and treatment periods, we measured the 24-hour ambulatory blood pressure (BP) and postural change of BP, and interviewed QOL. Terazosin treatment did not show consistent decrease of casual BP, but was associated with a transient decrease of systolic BP and an increase of pulse rate after standing, and enhanced postprandial decrease in BP. Nilvadipine decreased casual BP in a dose-dependent manner, but showed neither postural nor postprandial change of BP. There was no difference in QOL scores with either treatment. Results suggest that nilvadipine is preferable to terazosin for the treatment of elderly hypertensive patients with stroke.

Background and Objectives: The Japanese Red Cross Society recalled one lot of monoclonal-antibody-purified factor VIII (F VIII) and two lots of human serum albumin (HSA) 5 months after preparation of the final products, because of a procedural error that led to contamination by a unit of plasma positve for hepatitis B surface antigen (HBsAg). We evaluated the effectiveness of virus inactivation/removal in a large-scale process for manufacturing F VIII and HSA. Materials and Methods: HBV DNA in the retained samples in process was measured by the polymerase chain reaction (PCR). The kinetics of virus inactivation by solvent-detergent (S/D) treatment was examined using model viruses. We also did a look-back survey of the patients who received corresponding products. Results: Contaminated hepatitis B virus (HBV) DNA became undetectable beyond fraction S IV-I in the albumin process, and immunoaffinity chromatography in the F VIII process, respectively. The model viruses were inactivated within 5 s by S/D treatment. There is no evidence that patients were infected by HBV after transfusion of these products. Conclusion: We conclude that virus inactivation/removal was effectively achieved in a large-scale manufacturing process for F VIII and HSA.

A series of correlative studies show that sympathetic renal nerve activity (RNA) may be influenced by the concentration of sodium (Na+) in the plasma and the cerebrospinal fluid (CSF). Further study of the sites and characteristics of the interaction between Na+ and the renal nerves was undertaken in anesthetized dogs. Cerebroventricular (i.c.v.) injections of hypertonic sodium chloride (NaCl) produced a sympathetic vasoconstrictor response associated with tachycardia, increases in plasma norepinephrine and vasopressin (AVP), and a decrease in the electroneurographic activity recorded from post-ganglionic renal sympathetic nerves. Both bilateral vagotomy and intravenous administration of an AVP antagonist prevented the decrease in RNA caused by i.c.v. hypertonic NaCl, without markedly reducing the magnitude of the pressor response. The same phenomenon, however, could not be duplicated by delivery of the AVP antagonist i.c.v. In another group of dogs, the pressor activity of NaCl injected into the cisterna magna was compared before and after surgical ablation of the area postrema in the dorsal medulla. Removal of this circumventricular organ attenuated the pressor effects of NaCl given into the cisterna magna, but not those produced by i.c.v. delivery of the injectate. The data sugged that acute increase in CSF Na+ cause a differential activation of the sympathetic nervous system mediated in part by structures at or near the area postrema. At this site, circulating AVP apparently augments the inhibitory input from vagal afferents on the preganglionic renal nerve neurons.

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 19 cases with primary aldosteronism (PA) and 72 with essential hypertension (EHT) to differentiate the two disorders in the following conditions: 1) after overnight recumbency (basal state) and 2) after oral administration of captopril. Screening criteria were determined in order to pick up all of PA patients as positive. After the captopril administration, the specificity of a criterion based on the combination of PAC and PAC/PRA ratio was 93 % and positive predictive value 79 %. This criterion was superior to other conventional screening methods. However, higher specificity (97 %) and positive predictive value (90 %) were obtained from a combination criterion based on the basal PAC and PAC/PRA ratio. The single oral administration of captopril may not bring an improvement in the screening of PA.

Summary: The various enantiomeric esters of TFA-agr-amino acid may be separated directly by gas chromatography on optically active stationary phase. In this work we investigated the resolution of relatively volatile amino acids (alanine, agr-amino-n-butyric acid, valine, threonine, allo-isoleucine, isoleucine, norvaline, leucine, proline, norleucine, serine) and less volatile amino acids (cysteine, aspartic acid, methionine, phenylalanine, glutamic acid) on a glass capillary column coated with N-caproyl-L-valyl-L-valine cyclohexyl ester.

Summary The structural change of lignin during heating of wood was investigated quantitatively by a method combining nucleus exchange and nitrobenzene oxidation. Lignin modification during heating was mainly a diphenylmethane type condensation. About 40 and 75% of noncondensed units in protolignins were converted to diphenylmethane type units by heating of dry and wet wood meals up to 220 °C, respectively. On the other hand, during heating of modified lignin (dioxane lignin) various types of modifications in addition to diphenylmethane type condensation occurred. Lignin modification via the diphenylmethane type condensation was proposed as a new route for its utilization.

To evaluate the role of central nervous mechanisms and their relationships to the peripheral sympathetic nervous system in borderline hypertension, we measured catecholamines, angiotensin II (AII) and sodium (Na) concentrations in cerebrospinal fluid (CSF) with plasma catecholamines concomitantly in 12 young men with borderline hypertension and 7 age-matched healthy normotensive men on ordinary salt intake. Plasma norepinephrine (NE) and epinephrine (E) were higher in the borderline hypertensives than in the normotensives (NE: 239 ± 15 vs 190 ± 11 pg/ml, p < 0.05, E: 83 ± 9 vs 43 ± 6 pg/ml, p < 0.01). NE levels in CSF were also higher in the borderline hypertensives than in the normotensives (200±15 vs 150 ± 18 pg/ml, p < 0.05). In most of the subjects, CSF E and plasma and CSF dopamine levels were below the sensitivity of the assay. CSF NE correlated positively with both plasma NE (p < 0.01) and mean blood pressure (p < 0.05) in all subjects. Immunoreactive All and Na concentrations in CSF did not differ between the borderline hypertensives and normotensives. These results suggest that peripheral sympathoadrenal overactivity in young subjects with borderline hypertension may be related to an altered function of central noradrenergic neurons. A11 and Na in the central nervous system do not appear to have an important role in borderline hypertension

We conducted a study to determine the effect of exogenous cortisol on circadian blood pressure changes in patients with hypopituitarism. Under replacement with hydrocortisone of 15 to 25mg either once (8:00) or twice a day (8:00 and 20:00), and with prednisolone of 3.75 to 5mg once a day, the patients underwent non-invasive ambulatory blood pressure monitoring for 24 hours. The average 24-hour blood pressure before hydrocortisone replacement was 92.9±1.0 (systolic)/53.2±0.8mmHg (diastolic), while that after hydrocortisone replacement once or twice a day and prednisolone replacement significantly increased to 108.2±1.4/63.5±0.9mmHg, 109.1±1.6/62.3±1.0mmHg, and 105.4±1.2/62.3±0.9mmHg, respectively. Hydrocortisone replacement once a day showed a significant increase in day-night differences of blood pressure, while hydrocortisone replacement twice a day did not. There were no differences in nocturnal decrease in pulse rate between these two replacements. The daytime and nighttime urinary excretions of 17-hydroxycorticosteroids in hydrocortisone replacement once a day were 7.7mg/12hr (daytime) and 1.4mg/12hr (nighttime), respectively, while those in hydrocortisone replacement twice a day were 3.9mg/12hr (daytime) and 3.6mg/12hr (nighttime), respectively. Urinary 17-ketosteroids, epinephrine and norepinephrine did not show any differences between hydrocortisone replacement once and twice a day. These results suggest that hydrocortisone administration is one of the factors which modulate the circadian variation of blood pressure in patients with hypopituitarism, and may also suggest that the circadian change of cortisol secretion participates, at least in part, in the formation of an intrinsic circadian rhythm of blood pressure.

To clarify factors related to the QT interval prolongation produced by probucol, multivariate analysis was applied to clinical and laboratory data retrospectively obtained from 89 patients with hypercholesterolaemia, who had taken probucol for more than 3 months.

The synthesis and biological evaluation of three new sulfur-substituted oxidosqualene (OS) analogues (1−3) are presented. In these analogues, C-11, C-15, or C-18 in the OS skeleton was replaced by sulfur. The sulfur position in the OS skeleton was chosen to disrupt one or more key processes involved in cyclization:  (a) the folding of the B-ring into a boat conformation, (b) the anti-Markovnikov cyclization leading to the C-ring, or (c) the formation of the D-ring during the lanosterol biosynthesis. Enzyme inhibition kinetics using homogeneous mammalian oxidosqualene cyclases (OSC) were also examined for the previously reported S-19 analogue 4. The four analogues were potent inhibitors of mammalian OSCs (IC50 = 0.05−2.3 μM for pig and rat liver OSC) and fungal cell-free Candida albicans OSC (submicromolar IC50 values). In particular, the S-18 analogue 3 showed the most potent inhibition toward the rat liver enzyme (IC50 = 50 nM) and showed potent, selective inhibition against the fungal enzyme (IC50 = 0.22 nM, 10-fold more potent than the S-19 analogue 4). Thus, 3 is the most potent OSC inhibitor known to date. The Ki values ranged from 0.5 to 4.5 μM for pig OSC, with 3 and 4 showing about 10-fold higher potency for rat liver OSC. Interestingly, the S-18 analogue 3 showed time-dependent irreversible inhibition with homogeneous pig liver OSC (kinact = 0.06 min^-1) but not with rat OSC.

Twenty bedridden elderly patients with normal sleep-wake cycles were studied to evaluate the circadian variations of blood pressure, pulse rate, body core temperature, cortisol, and catecholamines with a focus on their relation to cerebral atrophy. Twenty-four-hour blood pressure (BP) and pulse rate monitorings were done with simultaneous measurement of urinary bladder temperature. Urine was also collected every 4 h to measure 17-hydroxycorticosterone and catecholamines. Based on the brain CT, frontal horn index (FHI: maximal distance between bilateral frontal horns/the corresponding width of the skull) was calculated as an index of cerebral atrophy. Analysis by the cosinor method revealed that the significant circadian rhythm with nocturnal decline was observed in only 9 patients (45%) for BP and in 13 patients (65%) for pulse rate. In contrast, 19 of 20 patients (95%) showed significant circadian rhythms of bladder temperature, with the nadirs appearing between 00:06 and 06:54. In the subgroup of mild cerebral atrophy (FHI < 0.30, n = 11), BP and pulse rate fell modestly but significantly during nighttime, whereas they did not fall in the subgroup of moderate to severe cerebral atrophy (FHI > or = 0.30, n = 9). The possibility could not be excluded that the sleep disturbance might result in the relatively high BP during nighttime. Bladder temperature, 17-hydroxycorticosteroids, and catecholamines showed significant nocturnal falls in both groups. In conclusion, nocturnal fall of BP disappeared in the bedridden elderly patients with cerebral atrophy, which cannot be explained by the change in the circadian variation of the sympathetic nervous system, cortisol, or body core temperature.

To determine whether E-643, a new a-blocking agent, would reduce the blood pressure, regardless of the posture, a 1 mg dose was given 3 times daily for 7 consecutive days, to 8 male and 7 female inpatients, aged 37–73 years, with essential hypertension. Blood pressure and pulse rate were measured daily in the supine, sitting and standing positions. Before and after the treatment with E-643, plasma levels of noradrenaline, adrenaline, dopamine-ß-hydroxylase, renin and aldosterone were determined, samples being obtained with the subjects recumbent and after standing upright for 60 min. A significant reduction in the systolic and diastolic blood pressures was evident in the supine (172±31/100±12 ? 151±28/89±14 mmHg), sitting (158±22/101±11 ? 138±28/89±15 mmHg) and standing (153±32/103±21 ? 129±31/89±20 mmHg) positions. The reduction in blood pressure remained unchanged throughout the period of administration of E-643. Pulse rate was not affected when the subjects were supine (67±10 ? 69±10 beats/min), but was increased in the sitting (68±10 ? 73±9 beats/min) and standing (73±10 ? 81±11 beats/min) positions. The increased pulse rate tended to decline during continued administration of E-643. Treatment with E-643 produced no significant change in plasma levels of adrenaline, noradrenaline, dopamine-ß-hydroxylase, renin and aldosterone. The antihypertensive effect of treatment was more prominent in the patients with higher levels of plasma catecholamines and dopamine-ß-hydroxylase, and was less prominent in those with higher plasma renin and aldosterone. Two patients had temporary bouts of dizziness and visual disturbances, but there were no subjective complaints during treatment.